The mechanism, or mechanisms, by which the local blood flow is regulated according to the needs of the tissues remains uncertain. Metabolic, nervous, myogenic, and humoral factors may all be involved. An understanding of this control system is essential to rational treatment and prevention of many diseases. We intend to test the proposition that there are several control mechanisms with separate inputs and separate pthways, and that in different muscles or tissues, in different species, and under certain conditions one mechanism may predominate and thus lend itself to analysis. Accordingly, we will use a variety of preparations from several species, but primarily auto-perfused, isolated, soleus (red) and gracilis (white) skeletal muscle of the cat. A number of parameters will be measured and/or controlled including tissue PO2, perfusion pressure, flow, and the content of gasses and other substances in the perfusion media. In innervated and denervated preparations we will look for autoregulatory responses as blood composition and metabolic demand are varied. Local responses seen in the visualized microcirculation of the gracilis preparation will be compared with the overall responses of the same muscle. To delineate mechanisms we will, in the visualized preparation, produce localized variations in the chemical environment combined with recordings of PO2 (intra and extra cellular) and other possible significant parameters. As mechanisms become apparent, or norms established, we will study animals in various pathological states, especially shock and hypertension and look for significant differences.